Different behavior of agmatine in liver mitochondria: Inducer of oxidative stress or scavenger of reactive oxygen species?

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• 作者：V. Battaglia ; C.A. Rossi ; S. Colombatto ; M.A. Grillo ; A. Toninello
• 关键词：Agmatine ; Mitochondria ; Reactive oxygen species ; Permeability transition
• 刊名：Biochimica et Biophysica Acta (BBA)/Biomembranes
• 出版年：2007
• 期刊代码：14_00052736
• 类别：bio
• 出版时间：May 2007
• 卷：1768
• 期：5
• 页码：1147-1153
• 文件大小：373 K

摘要

Agmatine, at concentrations of 10 μM or 100 μM, is able to induce oxidative stress in rat liver mitochondria (RLM), as evidenced by increased oxygen uptake, H₂O₂ generation, and oxidation of sulfhydryl groups and glutathione. One proposal for the production of H₂O₂ and, most probably, other reactive oxygen species (ROS), is that they are the reaction products of agmatine oxidation by an unknown mitochondrial amine oxidase. Alternatively, by interacting with an iron–sulfur center of the respiratory chain, agmatine can produce an imino radical and subsequently the superoxide anion and other ROS. The observed oxidative stress causes a drop in ATP synthesis and amplification of the mitochondrial permeability transition (MPT) induced by Ca²⁺. Instead, 1 mM agmatine generates larger amounts of H₂O₂ than the lower concentrations, but does not affect RLM respiration or redox levels of thiols and glutathione. Indeed, it maintains the normal level of ATP synthesis and prevents Ca²⁺-induced MPT in the presence of phosphate. The self-scavenging effect against ROS production by agmatine at higher concentrations is also proposed.